Single-electron transmetalation in organoboron cross-coupling by photoredox/nickel dual catalysis

Abstract

The routine application of Csp3-hybridized nucleophiles in cross-coupling reactions remains an unsolved challenge in organic chemistry. The sluggish transmetalation rates observed for the preferred organoboron reagents in such transformations are a consequence of the two-electron mechanism underlying the standard catalytic approach. We describe a mechanistically distinct single-electron transfer-based strategy for the activation of organoboron reagents toward transmetalation that exhibits complementary reactivity patterns. Application of an iridium photoredox catalyst in tandem with a nickel catalyst effects the cross-coupling of potassium alkoxyalkyl- and benzyltrifluoroborates with an array of aryl bromides under exceptionally mild conditions (visible light, ambient temperature, no strong base). The transformation has been extended to the asymmetric and stereoconvergent cross-coupling of a secondary benzyltrifluoroborate.

Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis

“…Product 4f is particularly striking, because the reaction manifold was shown to be selective for cross-coupling of aryl bromides in preference to aryl chlorides, offering yet another level of orthogonality and diversification. In general, functional group tolerance was found to be comparable with that reported for the related coupling with nonborylated aryl bromides (22) (Fig. 3).…”

“…This strategy would be enabled by our recently developed single-electron transmetalation manifold, wherein sp 3 -hybridized organoboron reagents participate in Ni-catalyzed cross-coupling through oxidative fragmentation to an alkyl radical promoted by an Ir photoredox catalyst (22)(23)(24). Our previous observation (22) that an sp 3 -hybridized organotrifluoroborate participates in photoredox/nickel dualcatalytic cross-coupling selectively in the presence of an sp 2 -hybridized organotrifluoroborate confirmed that the single-electron transmetalation activation mode is, indeed, orthogonal to the traditional two-electron regime under relevant reaction conditions. Furthermore, we were confident that the trivalent sp 2 -hybridized organoborons [pinacolboronate (BPin), neopentylglycolboronate (BNeop), and B(OH) 2 ] used in conventional cross-coupling reactions would be left intact during the course of the photoredox cross-coupling, because decomposition pathways, such as Significance Efficient assembly of small-molecule scaffolds is among the most fundamental goals of organic synthesis.…”

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…[57] In one of the seminal reports on dual Ir/Ni catalysis, Molander and co-workers disclosed an elegant cross-coupling manifold for the union of alkoxyalkyl-and benzyltrifluoroborates with aryl bromides. [57] Although only activated alkyltrifluoroborates were described in the initial study, the dual Ir/Ni catalysis system was subsequently successfully applied to the functionalization of unactivated secondary alkyltrifluoroborates. [58][59][60] The alkyl radical intermediates were formed through an oxidative activation process by SET between the alkyltrifluoroborate substrates and the excited-state Ir III * catalyst.…”

Decarboxylative C(sp3)–N cross-coupling via synergetic photoredox and copper catalysis

“…Thanks to the consequential advantages of alkyl carboxylic acids over alkyl halides in availability, stability and toxicity, the method and its underlying strategy are expected to have widespread uses in amine synthesis. The unique activity of copper-based catalysts in this decarboxylative C-N coupling contrasts the reign of nickel catalysis in analogous C-C coupling via tandem photoredox and metal catalysis 30,38,39 , underscoring their important divergences.…”

“…IV reacts with an aniline to give complex I and completes the metal catalytic cycle. This type of relay between photoredox catalysis and nickel catalysis has been exploited for C-C coupling 30,38,39 , and electron-transfer via photoredox catalysis is reported to promote C(sp 2 )-N reductive elimination 40,41 . However, a similar strategy has not been demonstrated for C(sp 3 )-N coupling.…”